Daniel J Cox’s research while affiliated with University of Virginia and other places

Background Type 2 diabetes (T2D) is a growing epidemic in the United States, and metabolic control has not been improved over the last 10 years. Glycemic excursion minimization (GEM) is an alternative lifestyle treatment option focused on reducing postnutrient glucose excursions rather than reducing weight. GEM has been proven to be superior to routine care when delivered face to face, and equivalent or superior to conventional weight loss therapy, but it has not been evaluated among patients newly diagnosed with T2D or in a self-administered format. Objective This pilot study evaluated the feasibility of a self-administered version of GEM, augmented with continuous glucose monitoring (CGM), to improve metabolic control (hemoglobin A1c [HbA1c]) while diminishing or delaying the need for diabetes medications in adults recently diagnosed with T2D. These primary objectives were hypothesized to be achieved by reducing carbohydrate intake and increasing physical activity to diminish CGM glucose excursions, leading to the secondary benefits of an increase in diabetes empowerment and reduced diabetes distress, depressive symptoms, and BMI. MethodsGEM was self-administered by 17 adults recently diagnosed with T2D (mean age 52 years, SD 11.6 years; mean T2D duration 3.9 months, SD 2.5 months; mean HbA1c levels 8.0%, SD 1.6%; 40% female; 33.3% non-White), with the aid of a 4-chapter pocket guide and diary, automated motivational text messaging, and feedback from an activity monitor, along with CGM and supplies for the 6-week intervention and the 3-month follow-up. Treatment was initiated with one telephone call reviewing the use of the technology and 3 days later with a second call reviewing the use of the GEM pocket guide and intervention. ResultsAt 3-month follow-up, 67% of the participants’ diabetes was in remission (HbA1c levels

Introduction We previously reported the physical, psychological and behavioral 3-month post-treatment results of a randomized controlled trial comparing glycemic excursion minimization (GEM) versus conventional weight loss (WL) therapy in the management of type 2 diabetes (T2D). GEM is a paradigm shift in the lifestyle management of T2D that focuses on reducing postnutrient glucose excursions, rather than reducing weight. We now present the 13-month follow-up results. Research design and methods The initial study sample of 172 were 30–80 years old, had T2D for ≤10 years, an HbA1c ≥6.8% (51 mmol/mol), and were not using insulin. Participants were randomized to 6 hours of group treatment, either to WL or one of three versions of GEM. GEM groups differed in degree of blood glucose (BG) feedback provided during treatment: no recommended feedback, systematic capillary BG feedback before and after nutrient intake and physical activity, or continuous glucose monitoring. Since these GEM groups did not differ in pre-post improvement they were combined for initial and current analyses. Of those who completed the 3-month postassessment, 100% and 96% of the WL and GEM participants completed the 13-month follow-up assessment. Results Pre to follow-up within-group comparisons indicated WL participants sustained improvement in body mass index (BMI) (−0.9±1.4, p=0.001). GEM participants continued to benefit in their HbA1c (−0.5±1.4, p<0.001), BMI (−1±1, p<0.001), high-density lipoprotein (p<0.001), reduction of carbohydrate ingestion (p<0.001), self-monitoring of blood glucose satisfaction (p<0.001) and frequency (p<0.001), diabetes knowledge (p<0.001), diabetes empowerment (p<0.001), and both diabetes distress emotional (p=0.009) and regimen (p=0.001) subscales. Forty-two percent and 52% of WL and GEM participants, respectively, were classified as responders (individuals whose A1c dropped by at least −0.5%), with a mean HbA1c reduction of −1.2% and −1.5%. Neither WL nor GEM responders differed from non-responders in baseline demographics, psychological or disease severity variables. While WL responders could not be predicted, 73% of GEM responders were predicted by post minus pretreatment reductions of HbA1c, diabetes medication and BMI. Conclusions While WL sustained improvement in BMI, GEM sustained benefits across a broad range of physical, behavioral and psychological parameters, beneficial for clinicians and adults with T2D. This may be especially relevant for primary care physicians who manage about 90% of patients with T2D. Trial registration number NCT03196895 .

BACKGROUND Type 2 diabetes (T2D) is a growing epidemic in the United States, and metabolic control has not been improved over the last 10 years. Glycemic excursion minimization (GEM) is an alternative lifestyle treatment option focused on reducing postnutrient glucose excursions rather than reducing weight. GEM has been proven to be superior to routine care when delivered face to face, and equivalent or superior to conventional weight loss therapy, but it has not been evaluated among patients newly diagnosed with T2D or in a self-administered format. OBJECTIVE This pilot study evaluated the feasibility of a self-administered version of GEM, augmented with continuous glucose monitoring (CGM), to improve metabolic control (hemoglobin A_1c [HbA_1c]) while diminishing or delaying the need for diabetes medications in adults recently diagnosed with T2D. These primary objectives were hypothesized to be achieved by reducing carbohydrate intake and increasing physical activity to diminish CGM glucose excursions, leading to the secondary benefits of an increase in diabetes empowerment and reduced diabetes distress, depressive symptoms, and BMI. METHODS GEM was self-administered by 17 adults recently diagnosed with T2D (mean age 52 years, SD 11.6 years; mean T2D duration 3.9 months, SD 2.5 months; mean HbA_1c levels 8.0%, SD 1.6%; 40% female; 33.3% non-White), with the aid of a 4-chapter pocket guide and diary, automated motivational text messaging, and feedback from an activity monitor, along with CGM and supplies for the 6-week intervention and the 3-month follow-up. Treatment was initiated with one telephone call reviewing the use of the technology and 3 days later with a second call reviewing the use of the GEM pocket guide and intervention. RESULTS At 3-month follow-up, 67% of the participants’ diabetes was in remission (HbA_1c levels <6.5%), and only one participant started taking diabetes medication. Participants demonstrated a significant reduction in HbA_1c levels (–1.8%; P <.001). Participants also experienced significant reductions in high-glycemic-load carbohydrates routinely consumed, CGM readings that were >140 mg/dL, diabetes distress, depressive symptoms, and BMI. Participants felt that use of the CGM was the most significant single element of the intervention. CONCLUSIONS GEM augmented with CGM feedback may be an effective initial intervention for adults newly diagnosed with T2D. A self-administered version of GEM may provide primary care physicians and patients with a new tool to help people recently diagnosed with T2D achieve remission independent of medication and without weight loss as the primary focus. Future research is needed with a larger and more diverse sample.

In a recent randomized clinical trial, we compared 6 hours of conventional weight loss (WL) training to an equivalent amount of Glycemic Excursion Minimization (GEM) that is a paradigm-shift in lifestyle management for adults with T2D. GEM focuses on diminishing post-nutrient BG excursions by: 1) minimizing BG upsurge by reducing net carbohydrate ingestion, and 2) hastening BG recovery by increasing routine and post-meal physical activity.1 We now present the 13-month follow-up data, with no further training or contact, to evaluate the relative durability of these interventions. All of the WL and 97% of GEM participants who completed 3-month post-assessment also completed 13-month follow-up. At 13 months, WL participants sustained the improvement in BMI they showed at 3 months, while GEM participants continued to significantly benefit from lower HbA1c (p<.001), diabetes medication usage, cardiovascular risk, BMI, HDL, and improved psychological function regarding empowerment and diabetes distress (p’s <.01). Fifty-two percent of GEM participants were classified as Responders (mean HbA1c reduction of -1.5%). Being a GEM Responder at 13 months was unrelated to demographic or disease severity variables. Regression analyses indicated being a GEM long-term Responder was preceded by short-term post-treatment reduction of HbA1c, BMI and diabetes medication, correctly classifying 76% of eventual Responders and Non-responders. WL Responders could not be identified. Our data suggest GEM is a sustainable treatment option in the management of T2D. 1BMJ Open Diabetes Research & Care, 8:e001795. doi: 10.1136/bmjdrc-2020-001795. Disclosure D. Cox: Research Support; Self; Abbott Diabetes, Dexcom, Inc. M. A. Moncrief: Research Support; Self; Abbott Diabetes, Dexcom, Inc. A. L. Mccall: None. Funding National Institutes of Health (DK108957)

Introduction This study of adults with type 2 diabetes employed a non-inferiority hypothesis to investigate whether an innovative lifestyle focused on minimizing postnutrient blood glucose (BG) excursions (glycemic excursion minimization (GEM)) would be equivalent or superior to conventional weight loss (WL) therapy in regard to reducing HbA1c, and superior to WL when investigating physical, behavioral and psychological secondary outcomes. The impact of BG feedback on GEM efficacy was also investigated. Research design and methods 178 adults with type 2 diabetes for ≤10 years, HbA1c ≥6.8%, and not using insulin were randomized to WL (n=40) or one of three versions of GEM. Didactic (GEM-D, n=39) taught participants to choose low-glycemic load foods, reduce sedentary time and increase moderate routine physical activity. GEM-S (n=51) received GEM-D and systematically measured BG before and after meals and physical activity to educate and motivate food and activity choices. GEM-C (n=48) received GEM-D with continuous glucose monitoring feedback. All participants received 6 hours of group training and BG and activity monitors. Before and 3 months after treatment, participants were assessed for HbA1c, lipids, weight, routine physical activity, nutrition, depression, diabetes empowerment and distress. Results GEM versions did not differ in primary or secondary outcomes, so they were combined for analyses. While WL reduced body mass index (BMI) (p=0.005), GEM demonstrated a greater reduction in HbA1c (p=0.005), BMI (p=0.013), carbohydrate intake (p=0.001), BG response to a glucose challenge (p=0.02), and cardiovascular risk (p=0.003). Only GEM participants significantly improved diabetes empowerment, diabetes distress, depressive symptoms, steps/day, and active hours and reduced calories/day. Neither intervention had negative side effects. Conclusions GEM is an effective alternative to WL with respect to physical, behavioral and psychosocial outcomes. Trial registration number NCT03196895 .

Objective: Attention-deficit/hyperactivity disorder (ADHD) confers elevated risk for automobile crashes, both as a clinical syndrome and continuously when examining risk as a function of symptom severity. However, the neurocognitive mechanisms and processes underlying this risk remain poorly understood. The current longitudinal study examined whether attention network components reflect neurocognitive pathways linking ADHD symptoms with adverse driving outcomes. Method: Drivers from six U.S. sites participating in the Strategic Highway Research Program Naturalistic Driving Study (N=3,226) were prospectively monitored for objectively identified crashes, near-crashes, and crash/near-crash fault. At study entry, drivers were assessed for ADHD symptoms; completed the Conners' Continuous Performance Test, Second Edition; and were then followed continuously for 1-2 years of routine, on-road driving using technology-enhanced in-car monitoring. Bias-corrected, bootstrapped mediation models examined the extent to which attention network components mediated the association between ADHD symptoms and future driving risk, controlling for known risk factors. Results: As expected, self-reported ADHD symptoms predicted all markers of future driving risk. Higher ADHD symptoms were associated with reduced inhibitory control, lower levels of top-down attentional control (endogenous orienting), and greater arousal decrements (phasic alertness). Controlling for ADHD symptoms, top-down attentional control uniquely predicted future crashes, near-crashes, and culpability for future crashes/near-crashes; only arousal decrements portended future near-crashes. Only top-down attentional control significantly mediated the association between baseline ADHD symptoms and future driving risk. Conclusions: The driving risks associated with ADHD appear to be conveyed in part by impairments in the top-down, voluntary control of attention, rather than by difficulties sustaining attention over time or inhibiting impulses, as is often assumed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

This study aimed to compare conventional medication management of Type 2 Diabetes (T2D) to medication management in conjunction with a lifestyle intervention utilizing continuous glucose monitoring to minimize glucose excursions. Thirty adults (63% female, mean age 53.3 years) who were diagnosed with T2D for &11 years (mean 5.6 years), had HbA1c ≥ 7.0% [51 mmol/mol] (mean 8.8%, [73 mmol/mol]) and were not using insulin, were randomized in a 1:2 ratio to Routine Care (RC) or four group sessions of Glycemic Excursion Minimization plus real-time CGM (GEMCGM). Assessments at baseline and 5 months included a physical exam, metabolic and lipid panels, a review of diabetes medications and psychological questionnaires. For the week following assessments, participants wore a blinded activity monitor and completed 3 days of 24-hour dietary recall. A subgroup also wore a blinded CGM. GEMCGM participants significantly improved HbA1c (from 8.9 to 7.6% [74 to 60 mmol/mol] compared with 8.8 to 8.7% [73 to 72 mmol/mol] for RC (p=.03). Additionally, GEMCGM reduced the need for diabetes medication (p=.01), reduced carbohydrate consumption (p=.009), and improved diabetes knowledge (p=.001), quality of life (p=.01) and diabetes distress (p=.02), and trended to more empowerment (p=.05) without increasing dietary fat, lipids or hypoglycemia. Confirming our prior research, GEMCGM appears to be a safe, effective lifestyle intervention option for adults with sub-optimally controlled T2D who do not take insulin.

Background: Weight loss (WL) is the initial treatment of choice for adults with t2d, but it is inappropriate for lean patients, unwanted/unsuccessful for some obese individuals, and unsustainable for others. An alternative is needed. Aim: Because post-prandial glucose (PPG) contributes strongly to A1c, we tested if a treatment focused on reducing PPG by reducing carbohydrate intake and increasing physical activity (Glycemic Excursion Minimization - GEM) would be equal or superior to WL for improving A1c and secondary benefits. We also hypothesized GEM would be enhanced by the quality and quantity of blood glucose (BG) feedback. Methods: Generally healthy adults (t2d ≤ 10 years, not on insulin, A1c ≥ 6.8) were randomized to WL (n = 36) or one of 3 GEM subgroups: 1) Didactic (GEMD, n = 35) taught participants how to choose low glycemic load foods, reduce sedentary time and increase moderate routine physical activity, 2) Didactic + systematic BG monitoring (GEMS, n =48) before and after meals and physical activity to educate, activate and motivate food and activity choices, or 3) Didactic + continuous glucose monitoring (GEMC, n = 43). WL treatment was led by diabetes nutritionists and followed the CDC Prevent T2 weight loss manual. GEM treatment was led by a diabetes nurse educator. All subjects received 6 hours of training, BG meters and wore activity monitors. A1c, weight, UKPDS, DDS, DES and PHQ-9 were assessed pre and 3 months post treatment. Results: The GEM subgroups did not differ, so they were combined. Both WL and GEM significantly reduced weight and diabetes distress (regimen). Only GEM significantly improved A1c (8.3 to 7.3, p <.001), cardiovascular risk (p <.001), empowerment (p <.001), and diabetes distress (emotional, p <.02). Discussion: Lifestyle interventions focused on minimizing PPG by reducing carbohydrates and increasing routine physical activity are effective alternatives to WL. Adding BG monitoring did not significantly enhance GEM’s effectiveness. Disclosure D. Cox: Research Support; Self; Dexcom, Inc. T. Banton: Research Support; Self; Dexcom, Inc. M.A. Moncrief: Research Support; Self; Dexcom, Inc. A. Diamond: Research Support; Self; Dexcom, Inc. V. Holmes: None. A. Wolf: None. K. Fang: None. A.L. McCall: None. Funding Dexcom, Inc. (IIS-2017-047); National Institutes of Health (R01DK108957)

This study compared newly licensed drivers with and without autism spectrum disorder (ASD) and experienced drivers. Twenty new drivers (8 with ASD) and 16 experienced drivers completed the Driving Attitude Scale (DAS) and drove a simulator and an instrumented vehicle. Heart rate (HR), galvanic skin response (GSR), wrist movement, eye-gaze and driving performance were monitored. ASD drivers had more negative attitudes toward driving and greater change in HR, GSR and wrist movement. In a driving simulator, drivers with ASD scored lower than NT drivers and were rated less safe. There were fewer differences during on-road driving. Poorer driving and greater anxiousness in the new drivers with ASD indicates the need for a large-scale study of driving performance and apprehension to formulate remediation.